Amblyopia, epidemiologically the most common vision impairment, is an ophthalmic condition usually beginning in early childhood and requiring immediate treatment in order for normal eye-brain visual pathways to develop. Most commonly unilateral, the cause of the problem in amblyopia is that, although there is no obvious structural abnormality in the eye, there is a problem with central fixation that can cause eccentric fixation in trying to see a target toward which the two eyes align or try to align. The anatomical centers of vision, the fovea and its most sensitive center the foveola (both contained in the macula) are so crucial to precise vision and visual stimulation that the further from the foveola that fixation occurs, the larger the compensatory or eccentric area must be. Although some eccentric areas can see surprisingly well, when vision is not central, a suppression scotoma, or area not seen by the eye, develops at or near the foveola, fovea or macula, getting worse as fixation moves further from the macula. Unless the scotoma is small enough for remaining central vision to compensate, which will not happen in the retinal periphery where Snellen equivalent visual acuity drops to 20/200 or worse outside the macula, the brain can start to suppress the image from the non-fixating eye, stopping the visual stimuli necessary to reach the visual pathways into the brain, arresting normal visual development and creating amblyopia. The drive for fusion necessary between the two eyes to see one image for stereo vision will not be sufficient. Amblyopia can be treated by interrupting binocular vision with occlusion of the sound eye, thereby stopping suppression of the amblyopic eye and allowing it to work. Significantly, without treatment, if the visual pathways in general do not develop, visual stimuli in later life will not compensate sufficiently for complete perception, nor will stereoscopic vision be possible. Although treatment does not guarantee stereoscopic vision, early and effective treatment increases the possibility of improving stereoscopic vision. Additionally, if amblyopia is left untreated and the sound eye becomes permanently damaged, for whatever reason, the amblyope will be forced to rely solely on the amblyopic eye. This reliance on the already visually impaired amblyopic eye can leave the amblyope with either blindness or serious vision loss.
For any binocular vision, the two eyes move in the same direction in order to see a target. With or without alignment of both eyes, each eye sees its own separate image(s) from the binocular retinal rivalry or disparity of the perceived images created by the distance between the two eyes, driving fusion to bring the images together in a way that the brain can interpret in a logical three dimensional or stereo perceptual image. With misalignment of the two eyes, such as with strabismus, and particularly in unilateral esotropia, a common cause of amblyopia, one eye does the work of central fixation. There are theories that amblyopia can develop in the crossing, non-fixating eye because either it experiences confusion during binocular vision trying to see images which overlap without accurate fusion between the two eyes, or the two eyes experience diplopia when unable to fuse. Over time, inability to fuse can cause the suppression of vision in the non-fixating eye which becomes amblyopic.
In completely cross-fixating bilateral strabismus, visual acuity might be equally good or bad between the eyes with no amblyopia, but there may be suppression, such that amblyopia could develop. The necessary developmental best corrected visual stimulation is obtainable during a long enough alternating period of central fixation, but bilateral strabismus patients must be monitored for the development of amblyopia. All strabismus patients must use best corrected vision, whether refractive error is spherical or astigmatic. Aligning or straightening the eyes with either prisms in the lenses or surgery is an important element of treatment in the course of strabismic management. Alignment, however, can cause secondary problems and will not conclusively correct amblyopia. Prisms also do not directly correct refractive error. Accommodative esotropes whose near vision can be corrected with a bifocal add to bring the converging fixating eyes' retinal images into better view in addition to their distance, usually hyperopic, correction, can do well but must be watched because amblyopia impairs the ability to control accommodation.
All amblyopes must have best corrected vision in both eyes for treatment to be effective. Other treatable problems, which must still be watched because of potential central suppression, include anisometropia, where the eye sizes can be markedly different, as in axial myopes who have longer eyes than hyperopes. The issue lies in best corrected vision, because, whether uncorrected or corrected the images produced are different sizes, a phenomenon known as aniseikonia, perceived best after correction of refractive error. Once corrected, the image is minified by lenses for treating myopia and magnified by lenses for treating hyperopia, so aniseikonia remains and is sharply and uncomfortably perceived, driving one eye to prefer fixation and creating amblyopia. Contact lenses can help, but careful instruction with parents and the patient is necessary continually and amblyopia can still develop. In some cases of smaller refractive differences known as isoametropia, eye sizes may make no difference, but binocular amblyopia can develop if refractive error is not corrected. If corrected early enough, normal fusion and stereopsis usually develop instead of amblyopia. Additionally, severe astigmatic refractive error can produce amblyopia along ametropic meridians, which may limit the effectiveness of astigmatic contact lenses in treating meridional amblyopes later in life.
Some of the most tragic and intractable forms of amblyopia are deprivational, such as a congenital cataract, even if removed at infancy and treated with contact lenses immediately and diligently. Corneal opacities, either congenital or early traumatic, sometimes can be treated surgically, but the best correction post-op such as with a contact lens does not often yield good vision. Corneal and any media opacity can lead to amblyopia. Ptosis, where the lid droops over the line of vision, can have better results with surgery. Retinal or optic nerve disorders, or any central brain disease or damage affecting the visual pathways, can lead to permanent uncorrectable vision loss or deprivation effects. Certain retinal and central brain diseases are not always detectable in early patient examinations, leading to treatment delay that can cause amblyopia. Another indication of amblyopia that can reduce visual acuity is nystagmus. In severe nystagmus, the eye cannot hold still long enough to focus though there may be improvement with amblyopia therapy. Regarding the various theories about amblyopiogenic mechanisms, other than deprivational causes or refractive errors, misalignment of the foveas appears to be a consistent cause of amblyopia. Amblyopic misalignment should be differentiated from monofixation and anomalous retinal correspondence. In all treatment plans, the clinician must ensure that the patient utilizes best corrected vision.
In most cases of amblyopia, there will never be development of full stereopsis, and fusion requires amblyopia treatment to make any progress. If treatment doesn't work, many amblyopes learn to rely on monocular cues to navigate the perspective of a three-dimensional world. One example of such a monocular cue is motion parallax, in which the patient observes the relationship between objects in the patient's field of view as the patient moves in relation to the objects. For example, when the patient moves and his or her perspective changes, objects that are closer to the patient appear to move more in relation to a distant background than objects that are further away.
Visual acuity describes several areas of visual thresholds, including spatial discrimination and minimum separable visual acuity. The ability of a patient to resolve spatial patterns is defined at the smallest visual angle at which the patient can discriminate two separate images or objects. Clinicians, however, prefer the concept of minimum separability, which is the angle that the smallest recognizable symbol subtends on the retina. Minimum separable acuity depends on two things, first, packing density of photoreceptors in the fovea. This is potentially related to amblyopia because of the possible phenomenon of the retinal spread of photoreceptors in some cases contributing to eccentric fixation and therefore causing amblyopia.
The second important consideration under the minimum separability category is object contrast. Contrast sensitivity is an important modern element for testing eye disease and treatment progress, as discussed in Pelli D G, Robson J G, Wilkins, A J., “The Design of a New Letter Chart for Measuring Contrast Sensitivity”, Clin. Vision Sci. 1988; 2:187-199 [Pelli-Robson], the contents of which are herein incorporated by reference.
The most commonly used and referred-to chart for testing visual acuity at both distance and near is a Snellen equivalent scale. The Snellen scale identifies normal visual acuity as the ability of a patient to resolve spatial patterns, usually tested by alpha-numeric characters, where each character as a whole subtends a visual angle of five minutes of arc at a distance from the patient of 20 feet (or 6 meters) at distance or 12 inches (or 33 centimeters) at near. For metric conversion, a type of standardized test chart can be placed at four meters and can also be used at one to two meters distance for the low-vision patient. The four meter chart leaves the patient 0.25D (diopters) myopic, which can be compensated for with a refractive lens at testing to correct to infinity at distance. Images or other non-literate testing techniques, such as those used in preferential looking, pointing responses, Allen cards, cover testing, HOTV matching, and the illiterate “E” test, are some of the methods used for testing younger, illiterate and non-verbal patients. Amblyopia can be under- or over-estimated in this patient group, making the treatment plan crucial to the improvement of amblyopia.
Snellen chart alpha-numeric systems do not change size in a mathematically exact progression except at the lower levels. Progression of letters using Snellen is a linear function, which is not a mathematically effective measuring system. Bailey and Lovie developed a logarithmic conversion chart known as the logarithm of the Mininum Angle of Resolution (“logMAR”). On logMAR charts, letter sizes progress geometrically, not linearly, using decimals that can easily be converted to Snellen (e.g., 0.0 is equivalent to 20/20). See Bailey I L, Lovie J E, New Design Principles for Visual Acuity Letter Charts. Am J Optom Physical Optics 1976; 53:740-5 [Bailey-Lovie].
Especially in the United States, many clinicians measure visual acuity on the Snellen scale. Normal visual acuity is described as “20/20”, where the numerator refers to the distance of the testing object from the patient in feet, and the denominator refers to the distance in feet at which the testing object subtends a visual angle of 5 minutes of arc. For example, if the patient is unable to resolve a spatial pattern at 20 feet (or its equivalent relative to the spatial pattern's size) that would subtend a visual angle of five minutes viewed at 60 feet (or its relative equivalent), the patient is said to have 20/60 visual acuity. One difficulty clinicians face in measuring visual acuity, especially in amblyopes, is the crowding phenomenon, also known as contour resolution or contour interaction, in which patients have difficulty resolving closely spaced contours and recognizing the patterns formed by the contours. For example, a patient may be able to recognize a single image in isolation at a smaller level of visual acuity than when the image is presented with other images. In amblyopes, the magnitude of the drop in measurable visual acuity in crowding situations can be larger than other patients. For purposes of visual acuity testing, even the interaction between a single symbol and the line formed by the edge of the chart can cause contour resolution problems and corresponding difficulties in accurately measuring visual acuity.
Traditionally, amblyopic patients have been treated by a process of occluding the patient's sound eye by covering the eye with the standard band-aid patch, the current usual standard of care. Such occlusion forces the amblyopic eye to work to resolve images, and therefore become stronger by developing the brain's visual pathways over time. Gradually, if compliance patching is successful, the visual acuity of the amblyopic eye can improve. Such treatment has been successful, but has significant drawbacks. The patches are uncomfortable, and until the vision in the amblyope's eye has recovered to normal visual acuity (if ever), the amblyope's reduced vision exposes the wearer to risks such as injury from not having peripheral vision on the patched eye to see approaching objects during normal activity. Because patch occlusion is normally used on young patients, wearing the patch can also expose the patient to teasing by other children. Other issues include skin irritations from the patch and the materials used to attach it. Because of these issues, patients frequently do not wear the patch for the full amount of time prescribed by the clinician, causing parental or guardian distress. This makes it difficult for a clinician to measure the amount of time that the patient's sound eye was actually occluded, known as the compliance time. The clinician must rely on the patient and the patient's parents to ensure that the patient wears the patch, and to estimate and report the actual compliance time. Patient and parent compliance estimates are notoriously unreliable, as either there is a general desire to please the clinician by reporting what the patient or parent thinks the clinician want to hear, or the patient and/or parent may give up estimating compliance time altogether. Because of these deficiencies, the clinician cannot determine the actual compliance time and is frustrated by the inability to accurately prescribe future treatment.
Other common methods of treatment include penalizing the patient's sound eye with a glasses lens with an incorrect prescription to defocus the sound eye. Using contact lenses is preferable once the techniques of wearing and cleaning has been mastered by the parents or an age-appropriate patient. For example, there are black lenses to completely occlude, which have the disadvantage of the patient knowing occlusion is occurring. Bilateral contact lenses, one to defocus and one to provide best corrected visual acuity can be used and switched on a schedule, but take vigilance to know which goes into which eye. It works most ideally in binocular amblyopes with similar refractive errors in each eye so that spares can be easily replaced. Another penalization method is the use of drugs such as atropine to cause the non-amblyopic eye to dilate and defocus. Lens penalization is undesirable because it is easy to circumvent by removing the glasses or contact lens. Drug penalization methods are not ideal because bioavailability, which varies from patient to patient, causes the drawback that the drug can affect other organs including the amblyopic eye, causing it to defocus, thereby increasing the risk of no improvement in the amblyopic eye, or worse, that the better eye becomes amblyopic. Variable bioavailability also reduces the amount of measurable clinical office data on the patient's improvement. The unpredictability of the correct dosage and application of the drug makes the correct prescription cumbersome for the clinician. Once again, the clinician must rely on the patient, or the patient's guardian for young children, to accurately apply the best-guess dosage.
Because there has been no way to accurately enforce or measure treatment compliance time with patch occlusion, lens or drug penalization, it has been very difficult for a clinician to judge the penalization in any form and prescribe accordingly. Current estimates of the necessary amount of compliance time for effective treatment vary widely, from minutes per day to hours. Similar issues exist with prescribing the correct duration and frequency of the occlusion therapy, which varies from patient to patient.
Fielder A R, Irwin M., Auld R, Cocker K D, Jones H S, Mosely M J, “Compliance In Amblyopia Therapy: Objective Monitoring Of Occlusion”, Br J Ophthalmol 1995; 79:585-589, [Fielder] describes one device designed to improve monitoring of patch compliance. Fielder discloses an occlusion dose monitor (“ODM”) that collected compliance data using a battery operated data-logger connected to the patient's patch. In Fielder, parents are still required to keep a parallel diary to monitor patch contact. Fielder notes that compliance is still difficult to measure and only discloses measuring compliance in the context of band-aid patching. Fielder does not disclose any interactive system for treating amblyopia, and Fielder's device shares the attendant disadvantages of band-aid patch occlusion as described above.
Interactive occlusive systems for the treatment of amblyopia are known in the art. See U.S. Pat. No. 4,726,672 to Diamond [Diamond I] and U.S. Pat. No. 4,896,959 to Diamond [Diamond II]. The amount of interactivity in such systems, however, is limited. Diamond I and II describe a system with LED displays limited to displaying characters that, through the use of mirrors and lenses, appear to be placed at a certain distance from the patient. The non-amblyopic eye is occluded using the device, and when the patient can recognize the displayed character, the patient must press a button to indicate which character was seen. As the treatment progresses, the patient is shown increasingly distant objects. Diamond I and II also require the patient to estimate the amount of time spent occluded and mail the occlusion time to the clinician. This complexity limits the use of the system to older patients, bypassing younger patients in which occlusion treatment is most effective. Also, using older, lower-risk patients requires fewer safeguards than younger patients, and despite showing some improvement in subjects with severe amblyopia, Diamond does not provide a representative sample of the population known to be in need of standard of care. The limited interactivity of the system also reduces the effectiveness of the therapy. The more the patient is mentally focused during the treatment, the harder the amblyopic eye will work, with potential improvement. The limited amount of characters displayed by the device also increase the risk that the patient will memorize the sequence of characters, or guess the correct character without actual recognition. Such limitations limit the ability of the clinician to rely on the results of the system. A further disadvantage of the Diamond systems is that the patient is aware when he or she has reached a certain target visual acuity level, because the patient is required to report the information to the clinician.
U.S. Pat. No. 5,206,671 to Eydelman, et al [Eydelman] describes an amblyopia treatment system using a personal computer for displaying various images to the amblyope, including pictures and cartoon images while the non-amblyopic eye is occluded. Eydelman also discloses the concept of using a video game to engage the patient's attention. Eydelman does not disclose, however, any form of occlusion other than the standard patch. While Eydelman discloses recording results, and monitoring and adjusting visual parameters, Eydelman does not disclose a method for precisely measuring occlusion compliance time. A further detriment to such systems is that with patch occlusion, the patient is conscious of which eye is occluded, which may limit the effectiveness of the treatment. Both the Diamond systems and the Eydelman system also require an auditory cue to the patient in order to indicate targeting success or failure, restricting use of the system by patients with hearing problems.
Previous interactive systems also suffer from a lack of safeguards on improper use. In order to meet or exceed the current standard of care, treatment systems must be very careful to avoid creating amblyopia in non-amblyopic eyes. This can occur either where the patient exceeds the recommended occlusion time for the non-amblyopic eye, or if the patient allows a non-amblyopic friend to use the treatment system. This concern is especially prevalent in younger patients.
Additionally, previously known interactive treatment systems utilize a standard downward progression of image size. Once the patient recognizes a character or an image at a certain visual acuity level, the next image or character is displayed at the next highest acuity level. This allows the patient to more easily memorize the progression of treatment, and may lead to a patient correctly guessing the correct image without actually achieving the indicated level of visual acuity.
Shutter-glasses are also known in the art for performing occlusion for treatment of eye disorders. U.S. Pat. No. 5,452,026 to Marcy [Marcy] describes a system for performing occlusion using LCD shutter glasses by connecting the LCD shutter glass for each eye to an independent timer system for occluding each eye according to independent duty cycles. Marcy, however, only discloses the use of the shutter glasses for occlusion as a treatment for improving stereopsis, not amblyopia, and furthermore does not suggest any mechanism for utilizing the shutter glasses in an interactive system for accurately measuring the compliance time and visual acuity.
The use of shutter glasses for simulating stereo vision in a computer application is also well known in the art. See U.S. Pat. No. 4,967,268 to Lipton [Lipton], the figures and specification of which are herein incorporated by reference. Lipton describes a system in which the user wears LCD shutter glasses where the shutter for each eye alternates between transparency and opacity according to a predetermined frequency above the human flicker fusion rate. The frequency at which the shutters are switched is synchronized with the display of visual frames by the computer, such that when the left shutter is opaque, the user is presented with the appropriate image for the user's right eye, and vice versa for the right shutter and left eye. In such a manner, the user's brain fuses the two images together to form one stereo image. Lipton does not disclose or suggest any application of the invention to treating amblyopia, or for measuring compliance time or visual acuity during treatment of amblyopia.
Furthermore, previous systems do not address the problem of crowding. In the real world, objects are not isolated as single images, and therefore systems that only treat amblyopia using single images do not accurately measure the patient's progress.
Because of the limitations of existing amblyopia treatments, there exists a continuing need for a fully interactive, individualized virtual reality occlusion system for treating amblyopia and precisely monitoring and recording compliance and visual acuity during such treatment.